title: Studies of the metabolic stability in cells of 5-(trifluoroacetyl)thiophene-2-carboxamides and identification of more stable class II histone deacetylase (HDAC) inhibitors.
abstract: 5-(Trifluoroacetyl)thiophene-2-carboxamides were found to be potent and selective class II HDAC inhibitors. This paper describes their further development and the investigation on the cause for the lack of cell-based activity. A rapid screening assay was set up which enabled the identification of more metabolic stable compounds as potent and selective class II HDAC inhibitors.
authors.affiliation: IRBM-Merck Research Laboratories Rome, Via Pontina km 30,600, Pomezia 00040, Rome, Italy. rita_scarpelli@merck.com
authors.forename: Rita
authors.initials: R
authors.lastname: Scarpelli
authors.forename: Annalise
authors.initials: A
authors.lastname: Di Marco
authors.forename: Federica
authors.initials: F
authors.lastname: Ferrigno
authors.forename: Ralph
authors.initials: R
authors.lastname: Laufer
authors.forename: Isabella
authors.initials: I
authors.lastname: Marcucci
authors.forename: Ester
authors.initials: E
authors.lastname: Muraglia
authors.forename: Jesus M
authors.initials: JM
authors.lastname: Ontoria
authors.forename: Michael
authors.initials: M
authors.lastname: Rowley
authors.forename: Sergio
authors.initials: S
authors.lastname: Serafini
authors.forename: Christian
authors.initials: C
authors.lastname: Steinkühler
authors.forename: Philip
authors.initials: P
authors.lastname: Jones
mesh_terms: D000577:Amides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001189:Aryl Hydrocarbon Hydroxylases / Q000037:antagonists & inhibitors; D065729:Cytochrome P-450 CYP2C9; D015195:Drug Design; D045325:HCT116 Cells; D006367:HeLa Cells; D022781:Hepatocytes / Q000187:drug effects; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases / Q000145:classification; D006801:Humans; D008862:Microsomes, Liver / Q000187:drug effects; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D013876:Thiophenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D014404:Tubulin / Q000187:drug effects
chemical_list: D000577:Amides; D056572:Histone Deacetylase Inhibitors; D013876:Thiophenes; D014404:Tubulin; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases; D006655:Histone Deacetylases